© 1989 Oxford University Press
research-article |
The Effect of Lifetime Sodium Saccharin Dosing on Mice Initiated with the Carcinogen 2-Acetylaminofluorene
*Division of Biochemica1 Toxicology1, National Center for Toxicological Research (HFT-110) Jefferson, Arkansas 72079
Division of Biometry, National Center for Toxicological Research (HFT-110) Jefferson, Arkansas 72079
Pathology Services Project, National Center for Toxicological Research (HFT-110) Jefferson, Arkansas 72079
Received March 28, 1988; accepted July 12, 1988
The Effect of Lifetime Sodium Saccharin Dosing on Mice Initiated with the Carcinogen 2-Acetylaminofluorene. FREDERICK, C. B., DOOLEY, K. L., KODELL, R. L., SHELDON, W. G , AND KADLUBAR, F. F. (1989). Fundam. Appl. Toxicol 12,346–357. sodium saccharin has been reported to promote the development of urinary bladder tumors in rats following low doses of several carcinogens. To evaluate the generality of this effect between species, an initiation-promotion study was conducted in mice. Weanling female BALB/c mice were initiated with 200 ppm dietary 2-acetylaminofluorene for 90 days. Following a 2-week period of control diet, saccharin was administered at 0, 0.1, 0.5, 1.0, and 5.0% in the diet for the remainder of the 132-week study. An elevated incidence of persistent bladder transitional cell hyperplasia and a low incidence of urothelial and hepatocellular tumors indicated that these organs achieved an adequate dose of the initiator. However, sodium saccharin dosing did not result in an increased incidence of tumors in either the bladder or liver and is therefore not considered to be a promoter of carcinogenesis at these sites in the mouse. Furthermore, sodium saccharin exhibited a modest inhibitory effect on the rate of development of lymphomas in both initiated and noninitiated animals. Interspecies differences in the bladder tumorigenic effect ofsodium saccharin and their association with differences in urinary tract physiology are discussed.